Obesity is a growing epidemic in the United States. The prevalence of obesity in adults has increased by over 75% since 1980, and, presently, more than half of the United States population is overweight, with nearly 1 in 3 adults being clinically obese. Obesity arises as a consequence of alterations in how the body regulates energy intake, expenditure, and storage. Recently, it has been suggested that the gut microbiota has an effect in energy extraction, hence obesity. Humans and mice harbor fewer Bacteroidetes and more Firmicutes than those of their lean counterparts. Also, fermenters and Methanobrevibacter smithii (a methanogen from the Archaea domain) appear to act syntrophically to affect energy uptake. Using high- throughput molecular methods, we confirmed that the microbiota of obese and normal-weight individuals differ and showed that the microbiota in patients following successful bariatric surgery are unique. Bariatric surgery is currently the only available treatment for morbid obesity that consistently achieves and maintains substantial weight loss, decreases the incidence and severity of obesity-related co-morbidities, and improves overall quality of life and survival. Based on our past work, we hypothesize that the dramatic change in the intestinal microbiota that occurs following RYGB may play a significant role in the success and/or eventual failure of RYGB. The primary goal of the proposed research is to assess the role of the human- intestinal microbial ecology on success or failure to lose weight following two common methods of bariatric surgery: the Roux-en-Y gastric bypass (RYGB) and the laparoscopic adjustable gastric band (LAGB). We will: 1) Use high-throughput sequencing to identify fermenters that interact with a particular group of H2-consuming microorganisms; 2) Track and quantify the presence of luminal and mucosal H2-consuming microorganisms using quantitative PCR; 3) Track metabolic products and determine syntrophies and metabolic functions of the microorganisms associated with energy extraction; and (4) Integrate and interpret the results using an ecological approach through mathematical modeling. Identifying the key syntrophic partnerships should reveal useful markers of obesity risk and successful weight loss following bariatric surgery. They also should lead to microorganism-based therapeutic strategies to improve the chance of success of bariatric surgery and other weight- loss approaches. PUBLIC HEALTH RELEVANCE: This project will investigate microorganisms that live in the human intestines and how they affect success or failure of weight loss after two methods of bariatric surgery. The ultimate goal is to find microorganisms that help weight loss following bariatric surgery.